Abstract

This study was designed to investigate whether genetic polymorphisms of the Wnt/β-catenin signaling pathway and its interactions are involved in the development of knee osteoarthritis (KOA). Patients with KOA (n = 131) and healthy individuals (n = 190) with different ancestry from two Mexican populations (Mexico City and Guadalajara City) were analyzed. Twenty-five SNPs from thirteen genes (WISP1, DKK1, SOST, FRZB, LRP1, LRP4, LRP5, LRP6, GSKB, ADAMTS5, GDF5, FMN2 and COL11A1) involved in the Wnt/β-catenin signaling pathway were genotyped. Genetic and allelic frequencies and gene–gene interactions were performed for this study. After adjusting for age, sex, BMI and admixture, significant associations were found for five SNPs in Mexico City: LRP6 rs12314259 (G/G genotype OR 0.22, P = 0.029; and G allele OR 0.48, P = 0.022), SOST rs851054 (C/T genotype OR 0.42, P = 0.027; and T allele OR 0.62, P = 0.026), FMN2 rs986690 (G/A genotype OR 0.42, P = 0.034; and A allele OR 0.50, P = 0.015), FRZB rs409238 (A/G genotype, OR 2.41, P = 0.022), and COL11A1 rs2615977 (A/C genotype OR 2.39, P = 0.024); no associations for Guadalajara City were found. With respect to gene–gene interactions, the pairwise interactions of WISP1–COL11A1, COL11A1–FRZB, FRZB–SOST and WISP1–FMN2 make it possible to visualize the synergistic or antagonistic effect of their genotypes or alleles in both populations. These results suggest that gene–gene interactions in the Wnt/β-catenin signaling pathway play a role in the etiology of KOA.

Notes

Funding

The study was funded by departmental resources.

Compliance with Ethical Standards

Conflict of interest

The authors declare that they have no conflict of interest.

Ethical approval

All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards. Informed consent was obtained from all individual participants included in the study.

Supplementary material

Supplementary Fig. 1. Inferred genetic ancestry of P1 and P2 subjects. A) STRUCTURE bar plot for k = 3 including the data of putative parental African (AFR), European (EUR) and Amerindian (AMR) populations. Each bar represents the genetic data from one individual, and the colors correspond to inferred ancestral population (AFR in green, EUR in blue and AMR in red). B) Structure ternary plot for P1 (orange) and P2 (yellow) subjects anchored by the three putative parental population (AFR in green, EUR in blue and AMR in red)—Supplementary material 1 (TIFF 127 KB)